Evidence map›Paper›PMID 38049801›Full record

ArticleMalaria journal2023

Human monoclonal antibodies inhibit invasion of transgenic Plasmodium knowlesi expressing Plasmodium vivax Duffy binding protein.

Quentin D Watson, Lenore L Carias, Alyssa Malachin, Karli R Redinger, Jürgen Bosch, Martino Bardelli, Lea Baldor, Lionel Brice Feufack-Donfack, Jean Popovici, Robert W Moon and 3 more

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.7field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 6 institutions in 3 countries.

Quentin D WatsonCenter for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Lenore L CariasCenter for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Alyssa MalachinCenter for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Karli R RedingerCenter for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Jürgen BoschCenter for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Martino BardelliDepartment of Biochemistry, University of Oxford, Oxford, UK.
Lea BaldorMalaria Research Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.
Lionel Brice Feufack-DonfackMalaria Research Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.
Jean PopoviciMalaria Research Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.
Robert W MoonFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Simon J DraperDepartment of Biochemistry, University of Oxford, Oxford, UK.
Peter A ZimmermanCenter for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA. paz@case.edu.
Christopher L KingCenter for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA. cxk21@case.edu.
Center for Global Health · USInstitut Pasteur du Cambodge · KHCase Western Reserve University · USUniversity of Oxford · GBLondon School of Hygiene & Tropical Medicine · GBVeterans Health Administration · US

Funding

Fetal Immunity to Falciparum MalariaR01AI064687 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI KING, CHRISTOPHER L · 2005 to 2015
$3.7M
Defining targets of protective immunity to vivax malaria using human monoclonal antibodiesR01AI143694 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI KING, CHRISTOPHER L · 2020 to 2024
$3.6M
Madagascar P. vivax Invasion of Duffy-negative Red CellsR01AI097366 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI ZIMMERMAN, PETER A. · 2013 to 2017
$3.6M
Immunology Training Program-PredoctoralT32AI089474 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI COBB, BRIAN A · 2010 to 2025
$3.4M
Primaquine metabolism and treatment of P. vivax in MadagascarR01AI148469 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI WILLIAMS, SCOTT MATTHEW, ZIMMERMAN, PETER A. · 2020 to 2023
$2.6M
Extent, dynamics and mechanisms of Plasmodium vivax immune evasion caused by PvDBP gene amplificationR01AI173171 · NIAID · INSTITUT PASTEUR DU CAMBODGE · PI Eugenia Lo, Jean POPOVICI · 2023 to 2026
$2.4M
Comprehensive characterization of the genetic factors and the host immune response associated to protection from clinical Plasmodium vivax malariaR01AI175134 · NIAID · INSTITUT PASTEUR DU CAMBODGE · PI TINEKE CANTAERT, Jean POPOVICI · 2023 to 2026
$2.3M
BLRD VA I01 BX001350Medical Research Council MR/M021157/1NIAID NIH HHS R01 AI064687NIAID NIH HHS R01 AI097366NIAID NIH HHS R01 AI143694NIAID NIH HHS R01 AI148469NIAID NIH HHS R01 AI173171NIAID NIH HHS R01 AI175134NIAID NIH HHS T32 AI089474NIH HHS 1R01AI173171NIH HHS AI064687
6 · The paper itself

Abstract

backgroundPlasmodium vivax has been more resistant to various control measures than Plasmodium falciparum malaria because of its greater transmissibility and ability to produce latent parasite forms. Therefore, developing P. vivax vaccines and therapeutic monoclonal antibodies (humAbs) remains a high priority. The Duffy antigen receptor for chemokines (DARC) expressed on erythrocytes is central to P. vivax invasion of reticulocytes. P. vivax expresses a Duffy binding protein (PvDBP) on merozoites, a DARC ligand, and the DARC: PvDBP interaction is critical for P. vivax blood stage malaria. Therefore, PvDBP is a leading vaccine candidate for P. vivax and a target for therapeutic human monoclonal antibodies (humAbs).

methodsHere, the functional activity of humAbs derived from naturally exposed and vaccinated individuals are compared for the first time using easily cultured Plasmodium knowlesi (P. knowlesi) that had been genetically modified to replace its endogenous PkDBP orthologue with PvDBP to create a transgenic parasite, PkPvDBPOR. This transgenic parasite requires DARC to invade human erythrocytes but is not reticulocyte restricted. This model was used to evaluate the invasion inhibition potential of 12 humAbs (9 naturally acquired; 3 vaccine-induced) targeting PvDBP individually and in combinations using growth inhibition assays (GIAs).

resultsThe PvDBP-specific humAbs demonstrated 70-100% inhibition of PkPvDBPOR invasion with the IC

conclusionThe PkPvDBPOR transgenic model is a robust surrogate of P. vivax to assess invasion and growth inhibition of human monoclonal Abs recognizing PvDBP individually and in combination. There was no synergistic interaction for growth inhibition with the humAbs tested here that target different epitopes or subdomains of PvDBP, suggesting little benefit in clinical trials using combinations of these humAbs.

Indexed as

Malaria VaccinesMalaria, VivaxPlasmodium knowlesiAnimalsAnimals, Genetically ModifiedAntibodies, ProtozoanAntigens, ProtozoanDuffy Blood-Group SystemErythrocytesHumansPlasmodium vivaxProtozoan ProteinsAntibodies, ProtozoanAntigens, ProtozoanDuffy Blood-Group SystemMalaria VaccinesProtozoan ProteinsA monoclonal antibodyDuffy antigenDuffy binding proteinPlasmodium knowlesiPlasmodium vivax

Identifiers

PMID38049801
PMCPMC10696754
OpenAlexW4389297361

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.